Novel Biologic Dupilumab Improves Eczema Symptoms

Phase III trials show significant benefits over placebo

Action Points

In two phase III trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo.

Note that atopic dermatitis is an immune-driven disease and the identification of helper T cell (Th2) upregulation as a key player led to the targeted, biologic treatment.

Results from the pivotal SOLO I and SOLO 2 trials confirm that the novel, investigational biologic drug dupilumab improves symptoms associated with atopic eczema in adults, including intense itching, anxiety, depression and anxiety.

In SOLO 1, 38% of patients who received the dupilumab injections every other week and 37% of patients who received the injections weekly met this primary outcome after 16 weeks, compared with 10% of those on placebo (P<0.001 for both comparisons with placebo).

Similar results were reported in the SOLO 2, with the primary outcome occurring in 36% and 36%, respectively, of patients receiving dupilumab injections weekly and every other week, and 8% of patients receiving placebo (P<0.001 for both comparisons) at 16 weeks.

The results were published Oct. 1 in New England Journal of Medicine in conjunction with a presentation at the European Academy of Dermatology and Venereology Congress in Vienna.

Dupilumab, which this week received priority review status from the FDA based largely on the findings from the phase III studies, is poised to become the first targeted systemic treatment for atopic dermatitis. The move means that an FDA ruling on the drug's approval should come no later than late March of next year.

Co-investigator Emma Guttman-Yassky, MD, PhD, of Icahn School of Medicine at Mount Sinai in New York City told MedPage Today that even though the biologic has not been compared head-to-head with cyclosporine, which is widely prescribed for severe eczema, it appears to have comparable efficacy with a much better safety profile.

"I do believe this drugs and other drugs that come from this research will revolutionize the treatment of atopic dermatitis," she said. "This is a chronic condition, and we need treatments that patients can stay on long term."

Guttman-Yassky said the recognition that, like psoriasis, atopic dermatitis is an immune-driven disease and the identification of helper T cell (Th2) upregulation as a key player led to the targeted, biologic treatment.

Dupilumab binds specifically to the interleukin (IL-4) receptor alpha (IL-4Rα) subunit of the IL-4 and IL-13 receptors, inhibiting signaling of both inflammatory cytokines.

They included adults with moderate-to-severe atopic dermatitis whose symptoms were not adequately controlled with topical treatments. The patients were randomized to 16 weeks of treatment with subcutaneous injections of dupilumab (300 mg) or placebo given either weekly or every two weeks alternating with placebo.

The primary outcome was the proportion of patients with a score of 0 or 1 (clear or almost clear) on the dermatologic disease severity score Investigator's Global Assessment (IGA) and a reduction of two points or more on the IGA score from baseline at week 16.

A total of 671 patients were enrolled in SOLO 1 and 708 patients were enrolled in SOLO 2.

Improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients treated with dupilumab than placebo (P<0.001 for all comparisons), and dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life.

Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups, but serious adverse events and events leading to treatment discontinuation were uncommon. Adverse events categorized as "infections and infestations" developed in 35%, 34% and 28% of patients receiving weekly dupilumab, biweekly dupilumab or placebo in SOLO 1, respectively and 28%, 29% and 32%, respectively in SOLO 2.

The most common adverse events in the two trials were exacerbations of atopic dermatitis, injection-site reactions and nasopharyngitis.

"The cause of conjunctivitis in patients with atopic dermatitis is not yet fully understood," the researchers noted. "In contrast to our findings in the current trials, the incidence of conjunctivitis was not increased in dupilumab-treated patients in earlier studies of dupilumab involving patients with asthma or with chronic sinusitis with nasal polyposis, which suggests that characteristics specific to atopic dermatitis may contribute to its cause."

A limitation cited by the researchers included the short treatment duration, which "did not address efficacy and safety of longer-term treatment."

"Results from larger trials of longer duration are needed to assess the effectiveness and safety of long-term treatment with dupilumab," they wrote.

The drug is to be marketed jointly upon approval by Regeneron Pharmaceuticals and Sanofi Genzyme.

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